Effects of Linomide on growth and metastasis of implanted human gastric cancer in nude mice

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Effects of Linomide on growth and metastasis of implanted human gastric cancer in nude mice

AIM: To elucidate the effect of angiogenesis inhibitor, Linomide, on tumor growth and metastasis in nude mice implanted with human gastric cancer.METHODS: A metastatic model of gastric cancer was established using orthotopic implantation of histologically intact tumor tissues into the gastric wall of nude mice. Linomide (0, 80, 160 mg·kg^-1) was given p.o. every day after the implantation, and the mice were sacrificed after 10 wk to detect tumor size and metastasis. The microvessel counts were measured by immunohistochemical staining using a monoclonal antibody against Human Factor VIII related antigen.RESULTS: Linomide treatment significantly decreased the size of the implanted tumors (control group: 1.36 ± 0.81 cm³vs Linomide treated group: 0.84 ± 0.51 cm³ and 0.62 ± 0.35 cm³, P < 0.05 and 0.01, respectively). Additionally, an antimetastatic effect of Linomide was clearly demonstrated in a dose dependent manner: mice given 80 mg·kg^-1 Linomide developed liver metastasis in 4 of 10 cases, mice given 160 mg/kg developed metastasis in only 1 of 10 mice, while it developed in 19 of 28 mice of the control group (P < 0.05 and 0.01, respectively). The number of metastatic foci was also significantly less in the treated group. Furthermore, the microvessel counts in tumors of treated mice was reduced by 33%-42% as compared with the control tumors (P < 0.01).CONCLUSION: Linomide has a strong inhibitory activity against in vivo tumor growth and metastasis of gastric cancer, effectively suppressing the growth of the primary tumor, preventing liver metastasis, and attenuating the rate of neovascularization.